Hereditary spastic paraplegia (HSP) is a genetically heterogenous group of inherited neurodegenerative disorders. Recently, an autosomal recessive form of HSP was mapped to 16q24.3, and subsequently the defective gene associated to HSP was identified and designated SPG7. The SPG7 gene product was predicted to encode a protein of 795 amino acids, and is called paraplegin. Paraplegin is highly homologous to a class of well studied yeast ATP-dependent zinc metalloproteases, which show 55%, 55% and 52% identity, respectively, to Afg3p, Rca1p and Yme1p. Mutation of either Afg3p, Rca1p or Yme1p in yeast results in pleiotropic effects with regard to growth, respiration and, particularly, in the assembly and/or degradation of more than one mitochondrial protein complex. Taking into account the homology of paraplegin to these yeast ATP-dependent zinc metalloproteases and what is known about their function, allows us to speculate as to what function paraplegin plays in normal individuals.